The broad objective of this application is to expand our knowledge of oncodevelopmental isozymes and isoproteins, in general, and of oncodevelopmental phosphatase isozymes in particular. To date we have observed three discrete developmental alkaline phosphatases in cancer cells maintained in culture and have observed modulation of their expression by prednisolone and n-butyrate. Similar patterns of expression have been observed in human tumor tissue, supporting the opinion that these phenomena are native to spontaneous tumors. If cancer is a disease of gene regulation as proposed by Markert and others then the ectopic expression of placental isozymes in tumors can be considered a direct reflection of this lack of regulation. Accordingly, it is our long-term objective to complete the definition of model systems in which to study regulation of developmental gene expression in normal cells and in tumors. The cell lines and their dominant alkaline phosphatase phenotypes are HeLa-TCRC-1 and HeLa 71 (term placental); HeLa D98AH2 (amnion/intestinal); DoT (non HeLa) (term placental); and Hs578T and MDA MB 157 (breast carcinoma, early placental/liver). The trophoblast cells bearing the tsA mutant of SV40 will provide normal gene expression at the non-permissive temperature and transformed gene expression at the permissive temperature (Chou). The isozyme characterization of the allelic gene products plus the GGT and HCG will be completed in relation to the modulation study and compared to choriocarcinoma. We expect to determine whether gene regulation is the same in the three populations of trophoblast cells and to compare the results in a corresponding series of hepatocytes. In this way, controls of expression of placental genes in neoplastic trophoblast versus neoplastic hepatocytes can be studied. The individual components to be examined of the mechanisms governing oncodevelopmental gene expression are messenger RNA, histone acetylation and chromatin-associated non-histone proteins.